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Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

Genetic Features of MAPT, GRN, C9orf72 and CHCHD10 Gene Mutations in Chinese Patients with Frontotemporal Dementia

Author(s): Xiang-Qian Che, Qian-Hua Zhao, Yue Huang, Xia Li, Ru-Jing Ren, Sheng-Di Chen, Gang Wang* and Qi-Hao Guo*

Volume 14, Issue 10, 2017

Page: [1102 - 1108] Pages: 7

DOI: 10.2174/1567205014666170426105713

Price: $65


Background: Mutations in microtubule associated protein tau (MAPT), progranulin (GRN), chromosome 9 open-reading frame 72 (C9orf72) and CHCHD10 genes have been reported causing frontotemporal dementia (FTD) in different populations. However, collective analysis of mutations in these four genes in Chinese FTD patients has not been reported yet.

Methods: The aim of this study was to investigate the genetic features of Chinese patients with MAPT, GRN, C9orf72 or CHCHD10 gene mutations in an FTD cohort recruited from multi clinical centers in Shanghai metropolitan areas, China. MAPT, GRN and CHCHD10 genes were analysed by direct sequencing, and C9orf72 hexanucleotide repeat expansion was analysed by repeat-primed PCR in 82 patients with sporadic FTD. The identified gene variants were screened in 400 age matched controls.

Results: We found one known pathogenic variant (rs63750959) and one novel mutation (NG_007398.1: g.120962C>T; H299Y) of MAPT gene, one novel variant (c.750C>A; D250E) of GRN gene and two novel mutations in CHCHD10 gene (c.63C>T, no AA change; c.71G>A, P24L). No abnormal C9orf72 gene hexanucleotide repeat expansion was identified in this cohort. Collectively, genetic testing could discover 4.9% sporadic FTD patients with genetic causes. In addition, MAPT and CHCHD10 might be more important genes affecting Chinese with FTD.

Keywords: MAPT, GRN, C9orf72, CHCHD10, frontotemporal dementia, Alzheimer.

Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 51(6): 1546-54. (1998).
Ferrari R, Hernandez DG, Nalls MA, Rohrer JD, Ramasamy A, Kwok JB, et al. Frontotemporal dementia and its subtypes: a genome-wide association study. Lancet Neurol 13(7): 686-99. (2014).
Cerami C, Scarpini E, Cappa SF, Galimberti D. Frontotemporal lobar degeneration: current knowledge and future challenges. J Neurol 259(11): 2278-86. (2012).
Rohrer JD, Guerreiro R, Vandrovcova J, Uphill J, Reiman D, Beck J, et al. The heritability and genetics of frontotemporal lobar degeneration. Neurology 73(18): 1451-6. (2009).
Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, et al. Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393(6686): 702-5. (1998).
Baker M, Mackenzie IR, Pickering-Brown SM, Gass J, Rademakers R, Lindholm C, et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 442(7105): 916-9. (2006).
Cruts M, Gijselinck I, van der Zee J, Engelborghs S, Wils H, Pirici D, et al. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 442(7105): 920-4. (2006).
DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72(2): 245-56. (2011).
Renton AE, Majounie E, Waite A, Simon-Sanchez J, Rollinson S, Gibbs JR, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72(2): 257-68. (2011).
van der Zee J, Gijselinck I, Dillen L, Van Langenhove T, Theuns J, Engelborghs S, et al. A pan-European study of the C9orf72 repeat associated with FTLD: geographic prevalence, genomic instability, and intermediate repeats. Hum Mutat 34(2): 363-73. (2013).
Rohrer JD, Rosen HJ. Neuroimaging in frontotemporal dementia. Int Rev Psychiatry 25(2): 221-9. (2013).
Bannwarth S, Ait-El-Mkadem S, Chaussenot A, Genin EC, Lacas-Gervais S, Fragaki K, et al. A mitochondrial origin for frontotemporal dementia and amyotrophic lateral sclerosis through CHCHD10 involvement. Brain 137(Pt 8): 2329-45. (2014).
Johnson JO, Glynn SM, Gibbs JR, Nalls MA, Sabatelli M, Restagno G, et al. Mutations in the CHCHD10 gene are a common cause of familial amyotrophic lateral sclerosis. Brain 137(Pt 12): e311. (2014).
Muller K, Andersen PM, Hubers A, Marroquin N, Volk AE, Danzer KM, et al. Two novel mutations in conserved codons indicate that CHCHD10 is a gene associated with motor neuron disease. Brain 137(Pt 12): e309. (2014).
Dols-Icardo O, Nebot I, Gorostidi A, Ortega-Cubero S, Hernandez I, Rojas-Garcia R, et al. Analysis of the CHCHD10 gene in patients with frontotemporal dementia and amyotrophic lateral sclerosis from Spain. Brain 138(Pt 12): e400. (2015).
Tang M, Gu X, Wei J, Jiao B, Zhou L, Zhou Y, et al. Analyses MAPT, GRN, and C9orf72 mutations in Chinese patients with frontotemporal dementia. Neurobiology of Aging 46: 2350-e11-4 (2016).
Jiao B, Xiao T, Hou L, Gu X, Zhou Y, Zhou L, et al. High prevalence of CHCHD10 mutation in patients with frontotemporal dementia from China. Brain 139(Pt 4): e21. (2016).
McKhann GM, Albert MS, Grossman M, Miller B, Dickson D, Trojanowski JQ, et al. Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick’s Disease. Arch Neurol 58(11): 1803-9. (2001).
Brooks BR. El escorial world federation of neurology criteria for the diagnosis of amyotrophic lateral sclerosis. subcommittee on motor neuron diseases/amyotrophic lateral sclerosis of the world federation of neurology research group on neuromuscular diseases and the el escorial “clinical limits of amyotrophic lateral sclerosis” workshop contributors. J Neurol Sci 124: 96-107. (1994).
Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 134(Pt 9): 2456-77. (2011).
Wojtas A, Heggeli KA, Finch N, Baker M, Dejesus-Hernandez M, Younkin SG, et al. C9ORF72 repeat expansions and other FTD gene mutations in a clinical AD patient series from Mayo Clinic. Am J Neurodegener Dis 1(1): 107-18. (2012).
Teyssou E, Chartier L, Albert M, Bouscary A, Antoine JC, Camdessanche JP, et al. Genetic analysis of CHCHD10 in French familial amyotrophic lateral sclerosis patients. Neurobiol Aging 42: 218 e1-3 (2016).
Baker M, Kwok JB, Kucera S, Crook R, Farrer M, Houlden H, et al. Localization of frontotemporal dementia with parkinsonism in an Australian kindred to chromosome 17q21-22. Ann Neurol 42(5): 794-8. (1997).
Chaussenot A, Le Ber I, Ait-El-Mkadem S, Camuzat A, de Septenville A, Bannwarth S, et al. Screening of CHCHD10 in a French cohort confirms the involvement of this gene in frontotemporal dementia with amyotrophic lateral sclerosis patients. Neurobiol Aging 35(12): 2884 e1-4 (2014).
Bjork VO, Ovenfors CO. The disc rotation in patients operated upon with the Bjork-Shiley tilting disc valves with radiopaque markers. Scand J Thorac Cardiovasc Surg 5(2): 83-6. (1971).
Chio A, Mora G, Sabatelli M, Caponnetto C, Traynor BJ, Johnson JO, et al. CHCH10 mutations in an Italian cohort of familial and sporadic amyotrophic lateral sclerosis patients. Neurobiol Aging 36(4): 1767 e3-6 (2015).
Kurzwelly D, Kruger S, Biskup S, Heneka MT. A distinct clinical phenotype in a German kindred with motor neuron disease carrying a CHCHD10 mutation. Brain 138(Pt 9): e376. (2015).
Auranen M, Ylikallio E, Shcherbii M, Paetau A, Kiuru-Enari S, Toppila JP, et al. CHCHD10 variant p.(Gly66Val) causes axonal Charcot-Marie-Tooth disease. Neurol Genet 1(1): e1. (2015).
Pickering-Brown S, Baker M, Bird T, Trojanowski J, Lee V, Morris H, et al. Evidence of a founder effect in families with frontotemporal dementia that harbor the tau +16 splice mutation. Am J Med Genet 125B(1): 79-82. (2004).
Boeve BF, Hutton M. Refining frontotemporal dementia with parkinsonism linked to chromosome 17: introducing FTDP-17 (MAPT) and FTDP-17 (PGRN). Arch Neurol 65(4): 460-4. (2008).
Kim EJ, Kwon JC, Park KH, Park KW, Lee JH, Choi SH, et al. Clinical and genetic analysis of MAPT, GRN, and C9orf72 genes in Korean patients with frontotemporal dementia. Neurobiol Aging 35(5): 1213 e13-7 (2014).
Jiao B, Tang B, Liu X, Yan X, Zhou L, Yang Y, et al. Identification of C9orf72 repeat expansions in patients with amyotrophic lateral sclerosis and frontotemporal dementia in mainland China. Neurobiol Aging 35(4): 936 e19-22 (2014).
Majounie E, Renton AE, Mok K, Dopper EG, Waite A, Rollinson S, et al. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurol 11(4): 323-30. (2012).
Millecamps S, Boillee S, Le Ber I, Seilhean D, Teyssou E, Giraudeau M, et al. Phenotype difference between ALS patients with expanded repeats in C9ORF72 and patients with mutations in other ALS-related genes. J Med Genet 49(4): 258-63. (2012).
Ogaki K, Li Y, Takanashi M, Ishikawa K, Kobayashi T, Nonaka T, et al. Analyses of the MAPT, PGRN, and C9orf72 mutations in Japanese patients with FTLD, PSP, and CBS. Parkinsonism Relat Disord 19(1): 15-20. (2013).
Mok K, Traynor BJ, Schymick J, Tienari PJ, Laaksovirta H, Peuralinna T, et al. Chromosome 9 ALS and FTD locus is probably derived from a single founder. Neurobiol Aging 33(1): 209 e3-8 (2012).
Smith BN, Newhouse S, Shatunov A, Vance C, Topp S, Johnson L, et al. The C9ORF72 expansion mutation is a common cause of ALS+/-FTD in Europe and has a single founder. Eur J Hum Genet 21(1): 102-8. (2013).
Ogaki K, Li Y, Atsuta N, Tomiyama H, Funayama M, Watanabe H, et al. Analysis of C9orf72 repeat expansion in 563 Japanese patients with amyotrophic lateral sclerosis. Neurobiol Aging 33(10): 2527 e11-6 (2012).

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